Canavan disease facts*

*Canavan disease facts medical author: Charles Patrick Davis, MD, PhD

Canavan disease is a gene-linked neurological disorder that results in brain tissue degeneration.

The cause of the disease is a genetic disorder that causes oligodendrocytes to remain immature and then die, thereby not completing the synthesis of myelin sheaths. The mutation is in the gene that synthesizes an enzyme called aspartoacyclase.

Symptoms of Canavan disease usually appear during the first 3 to 6 months of life and, unfortunately, progress rapidly. Symptoms include lack of motor development, abnormal muscle tone, difficulty feeding, and an abnormally large head that has poor muscle control. Some children develop paralysis, blindness, and/or hearing loss. These children are usually not active and appear apathetic.

Unfortunately, there is no cure or standard treatment for this disease. Treatment is symptomatic and supportive.

Death usually occurs before age 10 although few children may survive into the teens and early 20s. The prognosis is poor.

Research is ongoing. The gene for the disease has been located and there are animal models for this disease. Gene transfer to the brain, metabolic therapy to provide a missing metabolite (acetate), and enzyme therapy have yielded some encouraging results.

What is Canavan disease?

Canavan disease is a gene-linked neurological disorder in which the brain degenerates into spongy tissue riddled with microscopic fluid-filled spaces.

What causes Canavan disease?

Canavan disease has been classified as one of a group of genetic disorders known as the leukodystrophies. Recent research has indicated that the cells in the brain responsible for making myelin sheaths, known as oligodendrocytes, cannot properly complete this critical developmental task. Myelin sheaths are the fatty covering that act as insulators around nerve fibers in the brain, as well as providing nutritional support for nerve cells. In Canavan disease, many oligodendrocytes do not mature and instead die, leaving nerve cell projections known as axons vulnerable and unable to properly function. Canavan disease is caused by mutation in the gene for an enzyme called aspartoacylase, which acts to break down the concentrated brain chemical known as N-acetyl-aspartate.

What are the symptoms of Canavan disease?

Symptoms of Canavan disease usually appear in the first 3 to 6 months of life and progress rapidly. Symptoms include lack of motor development, feeding difficulties, abnormal muscle tone (weakness or stiffness), and an abnormally large, poorly controlled head. Paralysis, blindness, or hearing loss may also occur. Children are characteristically quiet and apathetic. Although Canavan disease may occur in any ethnic group, it is more frequent among Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians. Canavan disease can be identified by a simple prenatal blood test that screens for the missing enzyme or for mutations in the gene that controls aspartoacylase. Both parents must be carriers of the defective gene in order to have an affected child. When both parents are found to carry the Canavan gene mutation, there is a one in four (25 percent) chance with each pregnancy that the child will be affected with Canavan disease.

What research is being done on Canavan disease?

The gene for Canavan disease has been located. Many laboratories offer prenatal screening for this disorder to populations at risk. Scientists have developed animal models for this disease and are using the models to test potential therapeutic strategies. Three strategies are currently under investigation: gene transfer to the brain in order to replace the mutated gene for the enzyme; metabolic therapy to provide a crucial missing metabolite (acetate); and enzyme therapy where the enzyme aspartoacylase is engineered to be able to enter the brain and is injected in the the blood stream. Encouraging results have been obtained using these strategies.